Progressive osseous heteroplasia

Reviewed January 2009

What is progressive osseous heteroplasia?

Progressive osseous heteroplasia is a disorder in which bone forms within skin and muscle tissue. Bone that forms outside the skeleton is called heterotopic or ectopic bone. In progressive osseous heteroplasia, ectopic bone formation begins in the deep layers of the skin (dermis and subcutaneous fat) and gradually moves into other tissues such as skeletal muscle and tendons. The bony lesions within the skin may be painful and may develop into open sores (ulcers). Over time, joints can become involved, resulting in impaired mobility.

Signs and symptoms of progressive osseous heteroplasia usually become noticeable during infancy. In some affected individuals, however, this may not occur until later in childhood or in early adulthood.

How common is progressive osseous heteroplasia?

Progressive osseous heteroplasia is a rare condition. Its exact incidence is unknown.

What genes are related to progressive osseous heteroplasia?

Progressive osseous heteroplasia is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.

In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions. The protein produced from the GNAS gene is believed to play a key role in signaling pathways that help regulate the development of bone (osteogenesis), preventing bony tissue from being produced outside the skeleton.

The GNAS gene mutations that cause progressive osseous heteroplasia disrupt the function of the G protein and impair its ability to regulate osteogenesis. As a result, bony tissue grows outside the skeleton and causes the complications associated with this disorder.

Related Gene(s)

Changes in this gene are associated with progressive osseous heteroplasia.

GNAS

How do people inherit progressive osseous heteroplasia?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or "turned on," in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.

The GNAS gene has a complex genomic imprinting pattern. In some cells of the body the maternal copy of the gene is active, while in others the paternal copy is active. Progressive osseous heteroplasia occurs when mutations affect the paternal copy of the gene.

Where can I find information about diagnosis or management of progressive osseous heteroplasia?

These resources address the diagnosis or management of progressive osseous heteroplasia and may include treatment providers.

Genetic Testing Registry: Progressive osseous heteroplasia (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN034473)

You might also find information on the diagnosis or management of progressive osseous heteroplasia in Educational resources (http://www.ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about progressive osseous heteroplasia?

You may find the following resources about progressive osseous heteroplasia helpful. These materials are written for the general public.

MedlinePlus - Health information
Health Topic: Bone Diseases (http://www.nlm.nih.gov/medlineplus/bonediseases.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/109/resources/resources/1)
Educational resources - Information pages
Orphanet (http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=2762)
Patient support - For patients and families
- National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1046/viewAbstract)
- Progressive Osseous Heteroplasia Association (http://www.pohdisease.org/ABOUT_POH_DISEASE/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Progressive osseous heteroplasia (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN034473)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Ossification,%20Heterotopic%5BMAJR%5D)%20AND%20(progressive%20osseous%20heteroplasia%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/166350)

What other names do people use for progressive osseous heteroplasia?

Cutaneous ossification
Ectopic Ossification
ECTOPIC OSSIFICATION, FAMILIAL
Heterotopic Ossification
Osteodermia
Osteoma cutis
Osteosis cutis
POH

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about progressive osseous heteroplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding progressive osseous heteroplasia?

autosomal ; autosomal dominant ; bone formation ; cell ; cutaneous ; ectopic ; familial ; gene ; guanine ; imprinting ; incidence ; maternal ; mutation ; nucleotide ; ossification ; osteogenesis ; osteoma ; protein ; signal transduction ; skeletal muscle ; tissue ; transduction

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A. 2008 Jul 15;146A(14):1788-96. doi: 10.1002/ajmg.a.32346. (http://www.ncbi.nlm.nih.gov/pubmed/18553568?dopt=Abstract)
Aynaci O, Müjgan Aynaci F, Cobanoğlu U, Alpay K. Progressive osseous heteroplasia. A case report and review of the literature. J Pediatr Orthop B. 2002 Oct;11(4):339-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12370587?dopt=Abstract)
Chan I, Hamada T, Hardman C, McGrath JA, Child FJ. Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene. Clin Exp Dermatol. 2004 Jan;29(1):77-80. (http://www.ncbi.nlm.nih.gov/pubmed/14723729?dopt=Abstract)
Plagge A, Kelsey G, Germain-Lee EL. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol. 2008 Feb;196(2):193-214. doi: 10.1677/JOE-07-0544. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18252944?dopt=Abstract)
Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS. Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med. 2002 Jan 10;346(2):99-106. Erratum in: N Engl J Med 2002 May 23;346(21):1678. (http://www.ncbi.nlm.nih.gov/pubmed/11784876?dopt=Abstract)
Weinstein LS, Chen M, Liu J. Gs(alpha) mutations and imprinting defects in human disease. Ann N Y Acad Sci. 2002 Jun;968:173-97. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12119276?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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